Abstract 1797

Background:

Two consecutively performed randomized studies by the AMC evaluating chemoimmunotherapy for the treatment of HIV-associated NHL include AMC010 (Kaplan LD et al, Blood 2005: concurrent Rituximab [R] + CHOP vs. CHOP, N=150) and AMC034 (Sparano JA et al, Blood 2010: concurrent R+EPOCH vs. Sequential EPOCH → R; N=106). In AMC010, the addition of Rituximab to CHOP was associated with an increased risk of infectious death (15% vs. 2%, p=0.04) without a significant improvement in complete response (CR) rate (58% vs.47%; p=0.15), event free survival (EFS), or overall survival (OS). In AMC034, the CR rate met its primary efficacy endpoint in the concurrent arm (73%; 95% confidence intervals [CI] 58%, 85%) but not the sequential arm (55%; 95% CI 41%, 68%).

Methods:

We performed a pooled analysis of these two consecutive trials including patients treated with R-CHOP and concurrent R-EPOCH in order to determine the influence of the age-adjusted International Prognostic Index (aaIPI), CD4 count (< 100/uL vs. ≥ 100/uL), and treatment (CHOP vs. EPOCH) as variables on outcomes EFS, OS and CR.

Results:

The characteristics and outcomes of the study populations are shown in table 1. Patients treated with R-EPOCH tended to have better outcomes in both the low and high risk IPI groups. In a multivariate analysis that included pooled data from both consecutive studies, features that were significantly associated with improved EFS, OS, and CR rate included low aaIPI score and baseline CD4 count of at least 100/ul. Additionally patients treated with concurrent R-EPOCH exhibited improved EFS and OS even when adjusted for prognostic covariates including aaIPI score and CD4 count (table 2).

Conclusions:

These findings suggest that treatment outcomes may be superior with concurrent R-EPOCH compared with R-CHOP, and support the design of an ongoing phase III trial comparing concurrent R-EPOCH with R-CHOP in immunocompetent patients with diffuse, large B-cell lymphoma (NCT00118209). This analysis provides additional level 2 evidence supporting the use of concurrent R-EPOCH in patients with HIV-associated lymphoma. Acknowledgments: This study is presented on behalf of the AIDS Malignancy Consortium.

Table 1:

Patient characteristics and outcomes

R-CHOPR-EPOCH
No. 99 51 
CD4 > 100/uL 41% 31% 
High aaIPI risk (2-3 factors) 59% 69% 
Mean age (years ± standard deviation) 43.5 (± 8.3) 42.6 (± 8.4) 
CR rate:   
    Low risk aaIPI (0-1 factors) 76% (60%, 88%) 88% (62%, 98%) 
    High risk aaIPI (2-3 factors) 45% (32%, 58%) 60% (42%, 76%) 
2 year EFS:   
    Low risk aaIPI (0-1 factors) 57% (36%, 73%) 81% (51%, 93%) 
    High risk aaIPI (2-3 factors) 30% (18%, 43%) 59% (41%, 74%) 
2 year OS:     Low risk aaIPI (0-1 factors) 66% (43%, 82%) 87% (57%, 97%) 
    High risk aaIPI (2-3 factors) 36% (23%, 50%) 62%, (44%,76%) 
R-CHOPR-EPOCH
No. 99 51 
CD4 > 100/uL 41% 31% 
High aaIPI risk (2-3 factors) 59% 69% 
Mean age (years ± standard deviation) 43.5 (± 8.3) 42.6 (± 8.4) 
CR rate:   
    Low risk aaIPI (0-1 factors) 76% (60%, 88%) 88% (62%, 98%) 
    High risk aaIPI (2-3 factors) 45% (32%, 58%) 60% (42%, 76%) 
2 year EFS:   
    Low risk aaIPI (0-1 factors) 57% (36%, 73%) 81% (51%, 93%) 
    High risk aaIPI (2-3 factors) 30% (18%, 43%) 59% (41%, 74%) 
2 year OS:     Low risk aaIPI (0-1 factors) 66% (43%, 82%) 87% (57%, 97%) 
    High risk aaIPI (2-3 factors) 36% (23%, 50%) 62%, (44%,76%) 
View Large
Table 2:

Multivariate analysis regarding the outcomes event-free survival (EFS), overall survival (OS) and rate of complete or unconfirmed complete remission (CR/CRu)

EFS p-value HR (95% CI)OS p-value HR (95% CI)CR/CRu p-value HR (95% CI)
aaIPI score (0-1 vs. 2-3) <0.001 <0.001 <0.001 
0.32 (0.17, 0.57) 0.28 (0.14, 0.56) 4.58 (1.96, 10.69) 
CD4 (≥ 100 vs. < 100/uL <0.001 <0.001 <0.05 
0.42 (0.26, 0.69) 0.37 (0.22, 0.63) 2.70 (1.26, 5.79) 
R-EPOCH vs. R-CHOP <0.01 <0.01 0.117 
0.40 (0.23,0.69) 0.38 (0.21, 0.69) 1.90 (0.85, 4.22) 
EFS p-value HR (95% CI)OS p-value HR (95% CI)CR/CRu p-value HR (95% CI)
aaIPI score (0-1 vs. 2-3) <0.001 <0.001 <0.001 
0.32 (0.17, 0.57) 0.28 (0.14, 0.56) 4.58 (1.96, 10.69) 
CD4 (≥ 100 vs. < 100/uL <0.001 <0.001 <0.05 
0.42 (0.26, 0.69) 0.37 (0.22, 0.63) 2.70 (1.26, 5.79) 
R-EPOCH vs. R-CHOP <0.01 <0.01 0.117 
0.40 (0.23,0.69) 0.38 (0.21, 0.69) 1.90 (0.85, 4.22) 
View Large
Disclosures:

No relevant conflicts of interest to declare.

Topics:
cancer, chemotherapy regimen, cyclophosphamide, doxorubicin, prednisone, and vincristine, epoch protocol, hiv, lymphoma, non-hodgkin, rituximab, r-chop, uterine fibroids, complete remission

Author notes

*

Asterisk with author names denotes non-ASH members.

© 2010 by The American Society of Hematology
2010
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